The ability of animal to escape from the effects of vasopressin has been tested using a conscious unrestrained rat model. The rats are infused with vasopressin and fluids through an indwelling catheter. The initial phase of vasopressin escape is associated with increased urinary prostaglandin E2 excretion. Studies were undertaken to determine the physiological significance of this increased prostaglandin E2 excretion. Indomethacin was used to block the increase in prostaglandin E2 and the initial phase of vasopressin escape was abolished. Despite suppression of plasma renin activity there was no suppression of aldosterone. The physiological significance of this observation was evaluated with adrenalectomy and aldactone. The cyclic AMP system was evaluated with the measurement of cyclic AMP in dissected cortical collecting tubules and renal medullary and papillary tissue. The isolated perfused tubule will be used to clarify whether an alteration in intrinsic collecting tubular epithelial response to vasopressin underlies vasopressin escape.